Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives
Abstract
:1. Introduction
2. Capsaicin
First Author, Year [ref] | Experimental Design and Treatments | Results |
---|---|---|
In vitro studies | ||
Shang, 2017 [24] | Myoblast cells pre-exposed to capsaicin (50, 100 μM) overnight and then treated with LPS (100 μg/mL) | ↓ LPS-induced inflammation |
Vos, 2006 [26] | HEK293 cells transiently transfected with full--length TRPV1 and activated by capsaicin (1 µm) | ↓ TRPV1 channel function in a dose-dependent manner |
Animal studies | ||
Scheich, 2017 [28] | Chronic restraint stress-induced FM model | Compared to control group, RTX group: |
CD1 male mice (12-week-old, n = 9–11/group) | ↓ mechanical hyperalgesia | |
↑ basal noxious heat threshold | ||
Treatments: Capsaicin analogue RTX (10, 20, 70, 100 μg/kg) s.c. once daily for four consecutive days | ↔ anxiety, depression, or peripheral inflammatory changes | |
Human studies | ||
McCarty, 1994 [31] | Randomized double-blind, vehicle-controlled trial with primary | Compared to control group, capsaicin group: |
FM patients (n = 45, 44 women, 1 man) | ↑ grip strength at week 2 ↓ tenderness in tender points at week 4 | |
Treatments: capsaicin (0.025%) cream applied as thin layer to tender points on left or right side of upper body as directed by the tube label for 4 weeks | ↔ Visual Analog Scale of pain scores | |
↑ minor side effects including transient burning at application site | ||
Casanueva, 2013 [32] | Randomized controlled trial with FM patients | Compared to control group, capsaicin group: |
↑ desensitization to pain with repeated capsaicin application | ||
(n = 130, 126 women, 4 men) | ↓ Fibromyalgia Impact Questionnaire | |
↓ Fatigue Severity Scale scores | ||
Treatments: capsaicin (0.075%) cream applied topically over 18 tender points 3x/day for 6 weeks | ↓ myalgia score | |
↓ pressure pain threshold | ||
↓ role limitations due to emotional problems | ||
↓ Visual Analogue Scale of depression | ||
Chrubasik, 2010 [33] | Randomized double-blind, placebo-controlled trial with chronic soft tissue/back pain patients (n = 281, 174 women, 107 men) Treatments: capsaicin (0.05%) cream applied as a thin layer to painful area 3x/day for 3 weeks | Compared to control group, capsaicin group: |
↓ pain sum scores | ||
↑ minor side effects including local warmth and pruritis |
3. Ginger
4. Curcumin
5. Grape Seed Extract
6. N-3 Polyunsaturated Fatty Acids
7. Naringin
8. Genistein
9. Possible Molecular Mechanisms
10. Summary and Future Direction
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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First Author, Year [ref] | Experimental Design and Treatments | Results |
---|---|---|
In vitro study | ||
Ha, 2012 [36] | BV-2 cells were cultured and activated with LPS (1 mg/mL) for 12 h. LPS was removed from the cells and indicated 6-shogaol (1, 5, 10 μM) was added. NMMA, an inhibitor of iNOS enzyme activity, was used as a positive control | Compared to control group, 6-shogaol groups: |
↓ iNOS expression and release of NO | ||
↓ microglial activation | ||
Hosseinzadeh, 2017 [37] | C28I2 human chondrocytes pretreated with GE (5, 25 μg/mL) for 24 h, followed by incubation with IL-1β (10 ng/mL) for 24 h | Compared to vehicle group, GE groups: |
↑ anti-oxidant enzyme gene expression | ||
↓ reactive oxygen species | ||
↓ lipid peroxidation | ||
↓ Bax/Bcl ratio, inhibiting apoptosis | ||
↓ caspase-3 activity | ||
Animal studies | ||
Montserrat-de la Paz, 2018 [38] | Intermittent cold stress (ICS)-induced FM model | Compared to control group, GR groups: |
Female C57BL/6 J mice (n = 48, 5-week-old) | ↓ mechanical and thermal allodynia | |
↓ mechanical hyperalgesia | ||
Treatments: healthy control, ICS group, ICS + APAP (40 mg/kg/day), ICS + GR (0.5%, 1%), and ICS + GR (0.5%) + APAP (40 mg/kg/day) supplemented with standard diet for 8 weeks | ↑ improved behavioral changes related to cognitive disturbances associated with pain, anxiety, and depression ↓ proinflammatory mediators such as NO, PGE2, TXB2, IL-1β in LPS-stimulated macrophages | |
↑ synergism with APAP leading to further reduction in FM-like symptoms | ||
Fajrin, 2019 [39] | Complete Freud’s Adjuvant (CFA)-induced FM-like model | Compared to control group, RGO groups: |
Male mice (n = 48, 8-week-old) | ↓ hyperalgesia in a dose-dependent manner | |
Treatments: sham, negative control, RGO doses at 100, 200, 400 and 600 mg/kg orally 1x/day for 7 days | ↑ thermal response threshold | |
Abolaji, 2017 [40] | Chlorpyrifos (CPF)-induced FM-like model | Compared to the control group, 6-GRF groups: |
Female Wistar rats (n = 70, 100–125 g) | ↓ H2O2 and MDA levels | |
↑ catalase, SOD, GPX activity | ||
Treatments: control with corn oil only (2 mL/kg BW), 6-GRF (100 mg/kg BW), CPF dissolved in corn oil (5 mg/kg BW), CPF (5 mg/kg BW) and 6-GRF (50 mg/kg BW) concomitantly, CPF (5 mg/kg BW) and 6-GRF (100 mg/kg BW) concomitantly 1x/day for 35 days after CPF toxicity | ↓ NO, MPO, TNF-α | |
↓ caspase-3 | ||
Zhang, 2016 [41] | DSS-induced chronic colitis model | Compared to control group, GDNP group: |
Female FVB/NJ mice (n = 7, 6–8-week-old) | ↑ healing in wounded intestinal epithelial monolayers | |
↑ proliferation of IECs | ||
Groups including control with normal feeding and GDNPs 2 (300 μL of 1 mg/mL solution) by oral gavage 1x/day for 18 weeks | ↓ TNF-α, IL-6, IL-1β, MPO | |
↑ IL-10, IL-22 |
First Author, Year [ref] | Experimental Design and Treatments | Results |
---|---|---|
Animal studies | ||
Yang, 2017 [43] | Dextran sodium sulfate (DSS)-induced FM-like model | Compared to naive control group, curcumin group: |
Male SD rats (n = 57, 190–210 g) | ↓ visceral hyperalgesia in dose-dependent manner (no significant effect with lower curcumin dose) | |
Treatments: naive control, DSS + saline, and DSS + curcumin (20, 60 mg/kg) by oral gavage 1x/day for 10 days, beginning 3 days after initiation of DSS | ↓ TRPV1 expression in DRG neurons | |
↓ TRPV1 protein level in inflamed colon | ||
Zhi, 2013 [44] | Colorectal distension (CRD)-induced FM-like (VMR) model | Compared to vehicle group, curcumin group: |
↓ CRD-induced VMRs indicating a decrease in GI nociception | ||
Adult male SD rats (n = 4, 250–300 g) | ↓ visceral hyperalgesia | |
Treatments: control, vehicle, and curcumin (4 mg/kg⋅min) infusion for 3 min | ↓ TRPV1 activation in primary afferent neurons in concentration-dependent manner | |
Jejunal afferent firing in ex vivo jejunum preparations model | Compared to control group, curcumin groups: | |
Adult male Kunming mice (n = 25, 20–30 g) | ↓ TNBS-induced hypersensitivity of jejunal afferents | |
Treatments: control, curcumin at 1, 3, 10, and 30 μmol/L given extra- and intra-luminally in naïve and TNBS-treated mouse jejunum | ↓ capsaicin-induced rise in intracellular calcium and inward currents in mouse or rat DRG neurons | |
Fattori, 2015 [45] | KO2-induced superoxide anion-induced FM-like model | Compared to control group, curcumin groups: |
↓ mechanical and thermal hyperalgesia | ||
Male Swiss mice (25–30 g) | ↓ superoxide anion-induced leukocyte recruitment in peritoneal cavity | |
↓ MPO activity, oxidative stress, IL-1β and TNF-α production in paw skin | ||
Treatments: vehicle (2% DMSO in saline) i.pl., KO2 i.pl + saline s.c., KO2 i.pl. + curcumin (3, 10, or 30 mg/kg) s.c. 1 h before KO2 stimulus | ↓ NF-κB activation in paw skin | |
↑ IL-10 production, and HO-1 and Nrf2 mRNA expression in paw skin |
First Author, Year [ref] | Experimental Design and Treatments | Results |
---|---|---|
In vitro studies | ||
Fujishita, 2009 [47] | Oxidative stress-induced hippocampal neuronal cell death model | Compared to vehicle group, the GSE groups: |
Neurons treated with GSE (0–100 µg/mL) for 2, 6 and 12 h. Neurons pre-incubated for 24 h with GSE-treated ACM in presence or absence of anti-IL-6 antibodies (50 ng/mL). Then, neurons were stimulated with H2O2 in presence or absence of IL-6 with and without anti-IL-6 antibody for 2 h | ↑ mRNA expression of IL-6, COX-2, IL-1α, | |
in astrocytes with oxidative stress status | ||
Protected against neuronal death induced by | ||
oxidative stress | ||
Narita, 2011 [48] | Hippocampal neurons at 8 DIV treated with 50 µM glutamate for 30 min, in presence or absence of 0.01, 0.1, 1.0, or 10 ng/mL of GSE | Compared to vehicle group, the GSE groups: |
Protected Erk1/2 phosphorylation | ||
Protected dendritic arborization and augmented cell survival | ||
↓ caspase-3 activity | ||
Animal studies | ||
Mun, 2010 [42] | i.p. injection in gastrocnemius muscle of acidic saline-induced FM-like model | Compared to control group, proanthrocyanidin group: |
(n = 15) | ||
Female male SD rats (n = 15, 250–320 g) | ↑ anti-hyperalgesic effect in injected paw and contralateral paw | |
Treatments: control, acidic saline i.p. injection, oligomeric proanthrocyanidin complexes at 300 mg/kg injection i.p. on day 7 | ↓ expression of acid sensing ion channel 3 in brain M1 and motor cortex area | |
Xianchu, 2018 [49] | Exhaustive exercise-induced FM model | Compared to control group, GSPE-M and GSPE-H groups, |
↓ fatigue by prolonging the time to exhaustion in forced swimming test | ||
↓ lactic acid, LDH, and CK in serum | ||
Male ICR mice (n = 32, 8-week-old, 25 g) | ↓ MDA, TNF-α, and IL-1β in serum and skeletal | |
muscle of mice | ||
↑ SOD, CAT, and T-AOC in serum and skeletal | ||
Treatments: control, low-dose GSPE-L group (1 mg/kg/day), medium-dose GSPE-M group (50 mg/kg/day), and high-dose GSPE-H group (100 mg/kg/day) for 28 days | muscle of mice | |
↑ SDH and Na+-K+-ATPase activities in | ||
mitochondrial function of skeletal muscle | ||
Human study | ||
Edwards, 2000 [50] | Double-blind, randomized, crossover trial with moderate to severe primary FM (n = 12) | Compared to the placebo group, anthocyanidins at 80 mg daily group: |
Treatments: placebo, 40 mg, 80 mg, and 120 mg anthocyanidins daily. Each dose for 3 months | ↓ fatigue and sleep disturbance in 80 mg dose group |
First Author, Year [ref] | Experiment Design and Treatment | Results |
---|---|---|
Animal studies | ||
Veigas, 2011 [53] | Heat-induced FM-like model | Compared to SO group, CFO groups |
C57BL/6J male mice (n = 60) | ↓ sensitivity to heat induced pain in plantar paw region | |
Treatments: 4% regular fish oil diet (FO), 4% concentrated fish oil diet (CFO), 5% safflower oil diet (SO) ad libitum for 6 months | ↓ c-fos protein immunoreactivity and mRNA expression of ASIC1a, ASIC13, and TRPV1 in DRGs | |
Human study | ||
Fontani, 2010 [54] | Double-blind placebo-controlled design | Compared to placebo group, n-3 PUFA group: |
↓ pain intensity | ||
↓ number of positive tender points | ||
Treatments: placebo group (n = 23): 4 g of oleic sunflower oil daily for 35 days and n-3 PUFA group (n = 23): 4 g oil (2.8 g of omega-3 polyunsaturated fatty acids, EPA +DHA in a 2:1 ratio; 1,60 g EPA, 0.8 g DHA, 0.4 g of other types of omega-3 polyunsaturated fatty acids: alpha linolenic, stearidonic, eicosatetraenoic and ocosapentaenoic acid) daily for 35 days | ↓ pain intensity | |
↔ superficial thermal (heat and cold) | ||
↓ anger-hostility and depression↓ in AA/EPA, AA, cortisol↑ EPA, pain area (%) |
First Author, Year [ref] | Experimental Design and Treatments | Results |
---|---|---|
Animal studies | ||
Ben-Azu, 2019 [56] | Forced swim-induced FM-like model Male Swiss mice (n = 50) Treatments: vehicle (10 mL/kg BW, i.p.), naringin (2.5, 5 and 10 mg/kg BW, i.p.), diazepam (2 mg/kg BW, i.p.), donepezil (1 mg/kg BW, i.p.) and imipramine (15 mg/kg BW, i.p.) for 7 days | Compared to vehicle group, naringin groups: |
↑ locomotor activity | ||
↓ depressant and anxiety | ||
↑ % social preference | ||
↑ cognitive performance | ||
↓ AChE enzyme activity in brain | ||
↑ GSH, SOD, CAT levels in brain | ||
↓ MDA and nitrate levels in brain | ||
Pinho-Ribeiro, 2016 [57] | Acetic acid- and PBQ-induced FM-like visceral pain model Male Swiss mice Treatments: vehicle, Nar (16.7–150 mg/kg p.o.) given 30 min before stimulus Formalin-induced FM-like pain model Male Swiss mice Treatments: vehicle, Nar (50 mg/kg, p.o.) given 30 min before stimulus Capsaicin- and CFA-induced overt FM-like pain models Male Swiss mice Treatments: vehicle, Nar (50 mg/kg, p.o.) given 30 min before nociceptive stimulus. Carrageenan-, CFA-, capsaicin-, and PGE2-induced mechanical hyperalgesia Male Swiss mice Treatments: vehicle, Nar p.o. given 30 min before stimulus | Compared to vehicle group, Nar groups: |
↑ antinociceptive effect induced by acid, formalin, and capsaicin- and CFA | ||
↓ mechanical hyperalgesia induced by carrageenan, capsaicin, CFA, and PGE2 | ||
↑ NO/cGMP/PKG/ATP sensitive K+ channel signaling pathway | ||
↑ GSH production of plantar skin tissue | ||
↓ IL-33, TNF-α, IL-1β production, and NF-κB activation of paw skin tissues | ||
Zamanian, 2016 [59] | Exercise-induced fatigue-induced FM model Female Wistar rats (n = 50) Treatments: control, vehicle, 40, 80, and 160 mg naringin/kg/day for 30 days | Compared to vehicle group, naringin groups: |
↑ exhaustion swimming time | ||
↓ LDH activity and serum MMP-9 levels | ||
↑ blood glucose levels | ||
Xue, 2019 [60] | Hot plate-induced FM-like pain model | Compared to vehicle group, Nar groups: |
Acetic acid-, glutamate-, capsaicin-, capsaicin-, and formalin-induced FM-like pain models | ↑ antinociceptive effect against thermal and chemical-induced pain | |
Treatments: vehicles, Nar (25–75 mg/kg) p.o., before stimulus | ↓ capsaicin-induced paw licking number | |
Carrageenan-induced FM-like inflammatory model | ↓ carrageenan-induced peritoneal leukocyte infiltration of paw edema | |
Treatments: vehicles, Nar (25–75 mg/kg) p.o., given 30 min before stimulus | ↓ TNF-α, IL-1β, and IL-6 levels of skin |
First Author, Year [ref] | Experimental Design and Treatment | Results |
---|---|---|
Animal studies | ||
Lin, 2011 [61] | Acetic acid-induced FM-like pain model | Compared to vehicle group, genistein group: |
C57/BL6 mice (8–12-week-old) | ||
Treatments: vehicle treated with substance P (SP to induce current), genistein (30 µM), SP + genistein, SP + daidzein (30 µM) for 10 min on DRG neurons | ↓ SP-mediated inhibition of ASIC3-selective current and PTK activity of muscle dorsal root ganglion neuron | |
Jie, 2018 [68] | Glutamate-induced masseter muscle FM-like pain model | Compared to control group, genistein groups: |
↓ mechanical hypernociception at high genistein dose | ||
Female Sprague-Dawley OVX rats | Partially reversed E2-potentiated glutamate-evoked hypernociception of masseter muscle | |
Treatments: no injections (control); E2 vehicle + genistein, E2 + genistein vehicle, and E2 + genistein (2–60 mg/kg) for 12 days. | ↓ pNR2B and pERK1/2 expression in hippocampus |
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Shen, C.-L.; Schuck, A.; Tompkins, C.; Dunn, D.M.; Neugebauer, V. Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives. Int. J. Environ. Res. Public Health 2022, 19, 4148. https://doi.org/10.3390/ijerph19074148
Shen C-L, Schuck A, Tompkins C, Dunn DM, Neugebauer V. Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives. International Journal of Environmental Research and Public Health. 2022; 19(7):4148. https://doi.org/10.3390/ijerph19074148
Chicago/Turabian StyleShen, Chwan-Li, Alexis Schuck, Christina Tompkins, Dale M. Dunn, and Volker Neugebauer. 2022. "Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives" International Journal of Environmental Research and Public Health 19, no. 7: 4148. https://doi.org/10.3390/ijerph19074148